Identifying the mechanisms of leukemia progression
Identifying the mechanisms of leukemia progression
批准号:
10677759
负责人:
John D Crispino
金额:
$105.55万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-09-22 至 2028-08-31
关键词:
Acute Megakaryocytic LeukemiasAcute Myelocytic LeukemiaAdultAnimal ModelBiologyCRISPR screenChemopreventionChildhoodChildhood LeukemiaChromosome 21DevelopmentDiseaseDisparateDown SyndromeEventGATA1 geneGenesGeneticHematological DiseaseHematopoiesisHematopoieticLaboratoriesMalignant - descriptorMalignant NeoplasmsMegakaryocytesMutationMyelofibrosisMyeloproliferative diseasePathogenesisPathway interactionsPatientsPreleukemiaPrevention strategyRoleSamplingTumor Suppressor GenesWorkinsightleukemianew therapeutic targetnovel strategiesnovel therapeuticspreventtumor
中文摘要
点击翻译按钮获取中文摘要
英文摘要
PROJECT SUMMARY
Since 2002 when my laboratory discovered GATA1 mutations in all cases acute megakaryocytic leukemia in
children with Down syndrome, I have been at the forefront of defining the specific genetic events that promote
leukemia. I have extensively studied the role of GATA1 in normal and malignant hematopoiesis and gained many
insights into the contributions of several chromosome 21 genes, including DYRK1A, ERG and CHAF1B, in
leukemia. My laboratory is also well established in the field of the myeloproliferative neoplasms (MPNs),
especially in the role of megakaryocytes in the pathogenesis of myelofibrosis and the development of new
therapies for this disease. In this R35 application, I propose to focus my laboratory over the next 7 years (and
beyond) on understanding the mechanisms of leukemia progression from clonal hematopoietic disorders.
Specifically, we will identify and compare the ways that pediatric and adult disorders progress to acute myeloid
leukemia. We will leverage large scale CRISPR/Cas9 screening, animal models and primary patient samples to
deeply characterize the mechanisms of transformation and focus on answering three questions: 1) What are the
similar and disparate events that promote malignant progression of pediatric versus adult blood disorders? 2)
How does dysregulation of pathways downstream of identified tumor suppressor genes promote malignant
progression? 3) Which investigational or approved therapies can prevent progression or treat the tumors? The
answers to these questions will increase our basic understanding of cancer, reveal new therapeutic targets and
possibly shed light on chemoprevention strategies.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Gata1s mutant mice display persistent defects in the erythroid lineage.
GATA1S突变小鼠在红细胞谱系中显示持续的缺陷。
DOI:
10.1182/bloodadvances.2022008124
发表时间:
2023-07-11
期刊:
BLOOD ADVANCES
影响因子:
7.5
作者:
[Ling, Te, Zhang, Kevin, Yang, Jiayue, Gurbuxani, Sandeep, Crispino, John D.]
通讯作者:
Crispino, John D.
Identifying the pathways that drive progression of the MPNs to AML
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批准号:10307030
-
项目类别:
-
资助金额:$41.53万
-
财政年份:2021
-
负责人:John D Crispino
-
依托单位:
Aberrant megakaryopoiesis in the myleoproliferative neoplasms
-
批准号:10307918
-
项目类别:
-
资助金额:$13.15万
-
财政年份:2021
-
负责人:John D Crispino
-
依托单位:
Identifying the mechanisms of leukemia progression
-
批准号:10298553
-
项目类别:
-
资助金额:$107.7万
-
财政年份:2021
-
负责人:John D Crispino
-
依托单位:
Mechanisms of leukemogenesis in Down syndrome
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批准号:10307029
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项目类别:
-
资助金额:$12.56万
-
财政年份:2021
-
负责人:John D Crispino
-
依托单位:
Mechanisms of Leukemogenesis in Down Syndrome
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批准号:9913474
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项目类别:
-
资助金额:$22.83万
-
财政年份:2018
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负责人:John D Crispino
-
依托单位:
GATA1 Mutation in Defective Erythropoiesis
-
批准号:8651635
-
项目类别:
-
资助金额:$33.04万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
Aberrant Megakaryopoiesis in the Myeloproliferative Neoplasms
-
批准号:8707548
-
项目类别:
-
资助金额:$41.73万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
GATA1 Mutation in Defective Erythropoiesis
-
批准号:9115144
-
项目类别:
-
资助金额:$33.04万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
GATA1 Mutation in Defective Erythropoiesis
-
批准号:8737256
-
项目类别:
-
资助金额:$33.04万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
Aberrant megakaryopoiesis in the myeloproliferative neoplasms.
-
批准号:9922938
-
项目类别:
-
资助金额:$41.89万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
Aberrant Megakaryopoiesis in the Myeloproliferative Neoplasms
-
批准号:8581272
-
项目类别:
-
资助金额:$42.03万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
Aberrant megakaryopoiesis in the myeloproliferative neoplasms.
-
批准号:9240136
-
项目类别:
-
资助金额:$48.31万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
Aberrant megakaryopoiesis in the myeloproliferative neoplasms.
-
批准号:9922491
-
项目类别:
-
资助金额:$7.28万
-
财政年份:2013
-
负责人:John D Crispino
-
依托单位:
FASEB SRC on Hematopoietic Malignancies
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批准号:8199824
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2011
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负责人:John D Crispino
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依托单位:
Identification of Altered Molecular Signature of Down Syndrome iPS Cells
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批准号:7828943
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项目类别:
-
资助金额:$50.0万
-
财政年份:2009
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负责人:John D Crispino
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依托单位:
Role of Survivin in Development of Megakaryocytes and Erythroid Cells
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批准号:7921091
-
项目类别:
-
资助金额:$9.95万
-
财政年份:2009
-
负责人:John D Crispino
-
依托单位:
Identification of Altered Molecular Signature of Down Syndrome iPS Cells
-
批准号:7941752
-
项目类别:
-
资助金额:$49.93万
-
财政年份:2009
-
负责人:John D Crispino
-
依托单位:
Role of Survivin in Development of Megakaryocytes and Erythroid Cells
-
批准号:8060642
-
项目类别:
-
资助金额:$29.49万
-
财政年份:2007
-
负责人:John D Crispino
-
依托单位:
Role of Survivin in Development of Megakaryocytes and Erythroid Cells
-
批准号:7597114
-
项目类别:
-
资助金额:$30.09万
-
财政年份:2007
-
负责人:John D Crispino
-
依托单位:
Role of Survivin in Development of Megakaryocytes and Erythroid Cells
-
批准号:7388187
-
项目类别:
-
资助金额:$30.09万
-
财政年份:2007
-
负责人:John D Crispino
-
依托单位:
海外基金